Stressful environmental manipulation has been shown to influence in different ways the pathogenesis of neoplasia. The mechanisms involved remain undefined. Moreover, only limited information is available on the effects of prolonged exposure to environmental stress on tumor growth. Thus, in most previous studies, unrelated tumors in different species were subjected briefly to a single stress. The aim of the present proposal, by contrast, is to study in a single species (rats) the growth of a family of related tumors (4 lines of Morris hepatomas) and of their common, normal parent tissue (regenerating liver) during extended sojourn in a stressful environment. Thus, tumor-bearing rats will be exposed for 3 weeks to (a) high or (b) low ambient temperature, or (c) reduced barometric pressure. Additionally, other rats will receive (d) periodic injections of isoproterenol, a drug which induces some of the responses observed in stressed animals. The observed results will be correlated with the known biochemical charactristics of the hepatomas used, as well as with the hosts' food intake, to gain a clearer understanding of the mechanisms operating under these stress conditions.